Besifloxacin for acute bacterial conjunctivitis ·Meta-Analysis· Treating with besifloxacin for acute bacterial conjunctivitis: a Meta-analysis Jun-Jie Wang1, Xin-Yi Gao2, Hong-Zhuo Li3, Shan-Shuang Du2 1Changzhi Medical College, Changzhi 046000, Shanxi ● CONCLUSION: Besifloxacin is highly effective and safe Province, China for treatment of acute bacterial conjunctivitis. Further 2Shaanxi Ophthalmic Medical Center, Xi’an No.4 Hospital, comparative trials regarding the effect of besifloxacin Affiliated Guangren Hospital, School of Medicine, Xi’an for treatment of acute bacterial conjunctivitis will aid in Jiaotong University, Xi’an 710004, Shaanxi Province, China treatment decisions. 3 Heping Hospital Affiliated to Changzhi Medical College, ● KEYWORDS: besifloxacin; acute bacterial conjunctivitis; Changzhi 046000, Shanxi Province, China Meta-analysis; randomized controlled trials Co-first authors: Jun-Jie Wang and Xin-Yi Gao DOI:10.18240/ijo.2019.12.13 Correspondence to: Hong-Zhuo Li. Heping Hospital Affiliated to Changzhi Medical College, Changzhi 046000, Citation: Wang JJ, Gao XY, Li HZ, Du SS. Treating with besifloxacin Shanxi Province, China. [email protected]; Shan-Shuang for acute bacterial conjunctivitis: a Meta-analysis. Int J Ophthalmol Du. Shaanxi Ophthalmic Medical Center, Xi’an No.4 Hospital, 2019;12(12):1898-1907 Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China. INTRODUCTION [email protected] cute conjunctivitis, which is characterized by a self- Received: 2018-08-18 Accepted: 2019-09-25 A limited course of inflammation of the conjunctiva with persistent mucopurulent discharge, erythema and Abstract discomfort, is a contagious infection of the ocular surface that ● AIM: To evaluate the relative efficacy and safety of affects individuals ranging from neonates to the elderly. As besifloxacin for treatment of acute bacterial conjunctivitis. one of the most common eye disorders, acute conjunctivitis ● METHODS: A comprehensive search in PubMed, EMBASE can easily spread from one person to another, especially in Web of Science, Cochrane Central Database and CNKI situations in which individuals are in close personal contact, was undertaken for randomized controlled trials (RCTs) such as schools, daycare centers, and chronic health care comparing besifloxacin with other treatments or placebo. facilities[1-2]. The pathogens of acute conjunctivitis can be The primary outcome measures were clinical resolution, viral or fungal in nature; however, approximately 78% of rates of bacterial eradication, individual clinical outcomes, cases in children and half of cases in adults are caused by cure rates, and bacterial eradication rates of different bacteria. The most common causative bacterial species are kinds of pathogens. Safety outcomes were the number of Haemophilus influenza (H. influenza), Streptococcus pneumoniae adverse effects (AEs). The final search was performed on (S. pneumoniae), Staphylococcus aureus (S. aureus), and August 2018. Staphylococcus epidermidis (S. epidermidis)[3-4]. In fact, most ● RESULTS: Six RCTs were included. Four studies compared acute conjunctivitis cases are caused by several bacterial the efficacy and safety of besifloxacin with placebo, 1 species simultaneously, therefore, treatment often relies on study compared besifloxacin with moxifloxacin, and 1 clinical experience and is usually initiated with a broad- study compared besifloxacin with gatifloxacin. A total spectrum ophthalmic antibacterial treatment. Although acute of 2780 patients met the inclusion criteria. Besifloxacin bacterial conjunctivitis is a self-limited disease and can resolve presented higher efficacy and safety than did placebo in spontaneously due to the host’s immune factors in 1-2wk[5], clinical resolution, rates of bacterial eradication, individual topical ophthalmic antibiotics are warranted as they hasten clinical outcomes, cure rates, bacterial eradication rates clinical resolution and microbiological remission, decreasing of different kinds of pathogens and the number of AEs. the risk of relapse and the development of complications such There was no significant difference between besifloxacin as keratitis, orbital cellulitis, and panophthalmitis[1,6]. Classical and moxifloxacin or gatifloxacin in the comparison items antibacterials options include tobramycin, trimethoprim, mentioned above. ciprofloxacin, gatifloxacin and moxifloxacin[7]. However, the 1898 Int J Ophthalmol, Vol. 12, No. 12, Dec.18, 2019 www.ijo.cn Tel: 8629-82245172 8629-82210956 Email: [email protected] widespread use of broad-spectrum antibiotics has resulted in Study Identification Two investigators independently the emergence of resistance to those typical antibiotics[8-9]. identified articles using the eligibility criteria listed above. Therefore, developing new antibiotics with high efficacy and After reading the title and the abstract, if the investigators safety against some resistant bacteria is necessary. considered the articles potentially eligible, they would Besifloxacin is an advanced-generation fluoroquinolone subsequently read the full text. If there was any disagreement and represents the first chlorofluoroquinolone developed between the investigators, they discussed the issue with a third specifically for ophthalmic use. Unlike older fluoroquinolones investigator until they reached an agreement. that selectively target either DNA gyrase or topoisomerase Risk of Bias and Assessment of Study Quality The IV, besifloxacin has balanced activity against both of methodological quality of each eligible study was independently those enzymes[10-12]. In vitro studies have demonstrated determined by two investigators by using the Cochrane Risk of that its antibacterial capacity exceeds that of most other Bias tool, provided in the Cochrane Handbook of Systematic fluoroquinolones and nonfluoroquinolones, especially Reviews of Interventions (Version 5.3.0). The Cochrane risk against multidrug resistant Staphylococci[13-14]. Several of bias assessment tool includes the following items: sequence in vivo studies have also drawn optimistic conclusions generation (selection bias), allocation sequence concealment regarding the antibacterial potency of besifloxacin[15-16]. At (selection bias), blinding of participants and personnel present, besifloxacin ophthalmic suspension 0.6%, a long- (performance bias), blinding of outcome assessment (detection acting topical formulation using DuraSite technology (InSite bias), incomplete outcome data (attrition bias), selective Vision, Alameda, California) that helps retain therapeutic outcome reporting (reporting bias), and other potential sources doses of a drug on the surface of the eye, has been approved of bias. The authors’ judgment is categorized as “low risk”, in the United States, Canada, and various countries in Latin “high risk”, or “unclear risk” of bias. America, Europe, and Asia for the treatment of acute bacterial Data Extraction The two investigators analyzed the full conjunctivitis[17]. However, some data among in vivo studies text of all eligible articles and then extracted the following are contradictory, for example, Karpecki et al[15] found that information: study characteristics, publication years, number besifloxacin can eradicate S. pneumoniae more efficiently of participants allocated to each group, the mean age of each than placebo, while Silverstein et al[18] argued that the group, number of males and females in each group, the method of eradication rate of S. pneumoniae is not better than vehicle. intervention and the assessment time. If the two investigators Therefore, summarizing the data of published studies and disagreed with each other, they would ask for an opinion from drawing a general conclusion to guide the clinical application a third investigator until they finally came to a consensus. of besifloxacin are necessary. This review demonstrates the Statistical Analysis The two investigators found and recorded efficacy and safety of besifloxacin for treatment of acute parameters for following outcomes: clinical resolution, rates of bacterial conjunctivitis via Meta-analysis of randomized bacterial eradication, individual clinical outcomes, cure rates, placebo-controlled trials. We also compare the effect of bacterial eradication rates of different kinds of pathogens, and besifloxacin with other antibiotics if necessary. the number of AEs. MATERIALS AND METHODS Statistical analyses were carried out using RevMan 5.3 software. Search Strategy Two trained investigators performed an For all comparisons, odds ratios (ORs) and 95% confidence electronic literature search of major online databases, including intervals (CIs) were calculated as summary statistics for PubMed, Embase, Web of Science, Cochrane Central Database dichotomous variables. The mean difference (MD) and 95%CI and CNKI (all relevant studies were published in English or were calculated as summary statistics for continuous variables. Chinese with the date range from inception to August 31, P<0.05 was regarded as statistically significant. Statistical 2018). Key terms for searching the title and abstract included heterogeneity was quantified with the use of Chi-square (χ2) “besifloxacin”, “synaphymenitis”, “epipephysitis” and and I2 tests. Pooled summary statistics were calculated using a “conjunctivitis”. fixed-effect model ifsignificant heterogeneity was not detected. Eligibility Criteria Articles were included if they met the If heterogeneity existed